Trojan Microparticles Potential for Ophthalmic Drug Delivery

The administration of drugs to treat ocular disorders still remains a technological challenge in this XXI century. Although there is an important arsenal of active molecules useful to treat ocular diseases, ranging from classical compounds to biotechnological products, currenty, no ideal delivery system is able to profit all their therapeutic potential. Among the intraocular drug delivery systems (IODDS) proposed to overcome some of the most important limitations, microsystems and nanosystems have raised high attention. While microsystems are able to offer long-term release after intravitreal injection, nanosystems can protect the active compound from external environment (reducing their clearance) and direct it to its target tissues. In recent years, some researchers have explored the possibility of combining micro and nanosystems in “nanoparticle-in-microparticle (NiMs)” systems or “trojan systems”. This excellent idea is not exempt of technological problems, remains partially unsolved, especially in the case of IODDS. The objective of the present review is to show the state of art concerning the design, preparation and characterization of trojan microparticles for drug delivery and to remark their potential and limitations as IODDS, one of the most important challenges faced by pharmaceutical technology at the moment

Living oceans: making decisions from Early Childhood Education. A proposal to work Environmental Education from a Justice perspective

Irene Guevara Herrero - Universidad Autónoma de Madrid 0000-0002-8004-0402Beatriz Bravo Torija - Universidad Autónoma de Madrid 0000-0002-0739-9099José Manuel Pérez Martín - Universidad Autónoma de Madrid 0000-0002-0658-9050Recepción: 15.07.2020 | Aceptado: 30.09.2020Correspondencia a través de ORCID: Irene Guevara Herrero 0000-0002-8004-0402Adquirir la capacidad de tomar decisiones desde edades tempranas sobre problemas científico-tecnológicos y medioambientales se ha convertido en objetivo primordial en la educación científica. Para conseguirlo, resulta crucial presentar problemas cercanos al alumnado, cambiando el enfoque de la enseñanza de ciencias, desde la adquisición de conocimientos hacia su aplicación. Sin embargo, los problemas que se plantean en las aulas suelen ser globales como el cambio climático o la deforestación, y las soluciones sugeridas no suponen cambios de conducta. En este trabajo, se discute el diseño e implementación de una propuesta dirigida a Educación Infantil, centrada en la problemática del uso que hace el alumnado de los plásticos y las consecuencias para el medio ambiente. La implementación se realiza en un aula de 5 años, recogiéndose las producciones escritas de los alumnos, y considerando su capacidad para comprender el proceso de contaminación de los plásticos y reflexionar sobre el impacto que supone su uso excesivo. Los resultados muestran que los alumnos llegan a identificar el problema y reconocer su papel en el mismo, considerando entre otros el exceso de plástico que utilizan en su día a día, el recorrido de este desde su hogar al océano, y sus consecuencias.Acquiring the ability to make decisions on scientific-technological and environmental problems from an early age has become one of the main objectives in science education. To do so, it is crucial to present problems close to students, changing the focus of science teaching, from the acquisition of knowledge to its application. However, the problems that arise in classrooms are usually global, such as climate change or deforestation, and the suggested solutions do not involve behavioural changes. In this paper, we discuss the design and implementation of a proposal for Early Childhood Education, focused on students' use of plastics and the consequences for the environment. The implementation is carried out in a 5-year-old classroom, collecting the written productions of the students. We consider students’ ability to understand the process of plastic contamination and reflect on the impact of their excessive use. The results show that students come to identify the problem and recognize their role in it, considering, among others, the excess of plastic they use in their daily life, the route it takes from home to the ocean, and its consequences.Financiación: Esta investigación y la difusión de sus resultados está financiada por los proyectos de I+D+i EDU2017-82688-P (JMPM) y EDU2015-66643-C2-2-P (BBT), y se encuadra en la investigación que desarrollan IGH, BBT y JMPM en el marco de la Cátedra UNESCO en Educación para la Justicia Social en la Universidad Autónoma de Madrid

Haunted Houses, Social Spaces and Surveilled Homes: Scary and Sinister Places in Spanish Cinema (1999 - 2012)

Este artículo se centra en la representación visual y narrativa del espacio terrorífico en el cine español contemporáneo (1999 - 2012). Con la finalidad de observar el tratamiento de estos lugares siniestros en diferentes películas nacionales, se realiza un análisis textual cualitativo de nueve largometrajes , divididos en tres tipos de narrativas construidas en torno a lugares terroríficos o peligrosos: las casas encantadas donde habitan fantasmas, los espacios sociales (orfanatos y hospitales) en decadencia, y los hogares sometidos a la vigilancia de observadores externos. Los resultados demuestran que, en conjunto, las películas españolas analizadas construyen una imagen del hogar caracterizada por la inseguridad, la desconfianza, y el peligro, reflejando , en cierto modo , determinados acontecimientos que han marcado la historia reciente del país tales como la progresiva urbanización, la cr isis económica, los desahucios o la violencia doméstica.This article focuses on the visual and narrative representation of terrifying spaces in contemporary Spanish cinema (1999 - 2012). In order to observe the treatment of these sinister places in different Spanish films, a qualitative textual analysis of nine feature films is carried out, divided in to three different narratives regarding terrifying or dangerous places: haunted houses populated by ghosts, social spaces (orphanages and hospitals) in decay, and homes surveilled by external observers. The results show that, as whole, the Spanish films under discussion offer an image of the home characterized by insecurity, distrust and danger, reflecting somehow certain events that ha shaped the rec ent history of this country such as increasing urbanization, economic crisis, evictions or domestic violence

Casas encantadas, espacios sociales y hogares vigilados: lugares terroríficos y siniestros en el cine español (1999-2012)

This article focuses on the visual and narrative representation of abject spaces in contemporary Spanish cinema (1999-2012). Following Kristeva’s ideas (1982), the abject place is understood as locations where basic limits (the internal and the external, the private and the social, time continuity) are broken and the people who inhabit them are jeopardized or destroyed. This concept is explored through the qualitative analysis of nine film divided in three different narratives regarding dangerous or sinister places: haunted houses populated by ghosts, social spaces (orphanages and hospitals) in decay, and homes surveilled by external observers. The results show that, as whole, the Spanish films under discussion offer an image of the home characterized by insecurity, distrust and danger, reflecting somehow certain events that ha shaped the recent history of this country such as increasing urbanization, economic crisis, evictions or domestic violenceEste artículo se centra en la representación visual y narrativa del espacio abyecto en el cine español contemporáneo (1999-2012). Siguiendo a Kristeva (1982), el lugar abyecto se entiende como aquel donde se produce una ruptura de límites básicos (lo interno y lo externo, lo privado y lo social, la continuidad temporal) y que pone en peligro o destruye a quienes lo habitan. Se ilustra dicha noción a través del análisis cualitativo de nueve largometrajes divididos en tres tipos de narrativas construidas en torno a lugares siniestros o peligrosos: las casas encantadas donde habitan fantasmas, espacios sociales (orfanatos y hospitales) en decadencia, y hogares sometidos a la vigilancia de observadores externos. Los resultados demuestran que, en conjunto, las películas españolas analizadas construyen una imagen del hogar caracterizada por la inseguridad, la desconfianza, y el peligro, reflejando en cierto modo determinados acontecimientos que han marcado la historia reciente del país tales como la progresiva urbanización, la crisis económica, los desahucios o la violencia doméstica

Simultaneous co-delivery of neuroprotective drugs from multiloaded PLGA microspheres for the treatment of glaucoma

Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ± 1.89 μm rendering them suitable for intravitreal injection using conventional 25G-32G needles. Greater than 62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC50 10.00±0.94 mM versus 6.89±0.82 mM in absence of DMQ-MSs) in R28 cell line. In vivo efficacy studies were performed using a well-established rodent model of chronic ocular hypertension (OHT), comparing single intravitreal injections of microspheres of DMQ-MSs to their equivalent individual single drug loaded MSs mixture (MSsmix), empty MSs, no-treatment OHT only and naïve groups. Twenty one days after OHT induction, DMQ-MSs showed a significantly neuroprotective effect on RGCs compared to OHT only controls. No such protective effect was observed in empty MSs and single-drug MSs treated groups. This work suggests that multi-loaded PLGA MSs present a novel therapeutic approach in the management of retinal neurodegeneration conditions such as glaucoma

¿Cómo enseñar la Prehistoria en Educación Infantil? Ideas y recursos de los docentes en formación

Prehistory is a period over which has spread numerous alternative ideas, turn there are few studies on how this content is addressed in the different educational stages, especially in Early Childhood Education. Therefore, as part of a multidisciplinary project on how to work this historical period with children, we analyzed on the one hand, what alternative ideas handle 186 future teachers before and after performing the project; and on the other, if they identify what resources are considered valid to work with Prehistory in Childhood Education and the potential of this historical period as interdisciplinary context. Data was collected through pre and posttest questionnaires, and the responses were analyzed qualitatively and quantitatively. The results showed that there are changes in the perception that future teachers have about Prehistory, they start recognizing Prehistory as an interdisciplinary context and become more critical selecting the resources for their teaching.La Prehistoria es un periodo sobre el que se han difundido numerosas ideas alternativas, existiendo escasos estudios sobre cómo se aborda su enseñanza en las diferentes etapas educativas, en especial en Educación Infantil. En el marco de un proyecto multidisciplinar sobre cómo se trabaja este periodo histórico durante la formación docente, analizamos, por una parte, qué ideas alternativas poseen 186 futuros maestros y maestras antes y después de realizar el proyecto; y por otra, si identifican qué recursos consideran válidos para trabajar la Prehistoria, en Educación Infantil y la potencialidad de este periodo histórico como contexto interdisciplinar. Los datos se recogieron a través de cuestionarios pre y post test, y sus respuestas se analizaron cualitativa y cuantitativamente. Los resultados mostraron que se producen cambios en la percepción que tienen los futuros maestros sobre la Prehistoria reconociéndola como un contexto interdisciplinar y volviéndose críticos al seleccionar los recursos para trabajarla

Promoviendo la Didáctica de la Educación Ambiental mediante una propuesta que fomenta el razonamiento científico-matemático

La Educación Ambiental cuenta con una larga trayectoria histórica con un marcado enfoque teórico y poco didáctico. Por ello, actualmente existen grandes limitaciones en las prácticas educativas, posiblemente derivadas de la escasa atención que se le ha proporcionado a la formación docente. Tratando de repensar esta formación, resulta necesario elaborar y difundir propuestas didácticas, para que,implementándolas, doten a los futuros maestros y maestras de vivencias y herramientas que les permitan implementar actuaciones de éxito en sus aulas. En este artículo se presenta una actividad basada en la argumentación y el uso de pruebas, en formato de tablas y gráficos, para trabajar el lenguaje científico-matemático en el contexto del desplazamiento y sustitución de especies en un ecosistema. Además, se analizan las destrezas científico-matemáticas que deben poner en juego los docentes en formación al trabajar la propuesta diseñada y se valora el potencial didáctico de la actividad para promover una Educación Ambiental desde una perspectiva transformadora. En general, la actividad promueve la aplicación de destrezas básicas, de investigación y comunicativas y fomenta la formación de una ciudadanía y un colectivo docente informados, reflexivos, críticos y participativos.Este trabajado ha sido realizado gracias al contrato de investigación predoctoral FPI-UAM (IGH) y a la estancia predoctoral en la UDIMA (IGH y JRG), en el marco del proyecto de transferencia Teachers as Environmental Learning Hub: Biodiversidad Urbana 2022/0375 – Programa: 465059 (IGH, JMPM, BBT).2022-2

Genes and variants underlying human congenital lactic acidosis—from genetics to personalized treatment

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, los autores pertenecientes a la UAM y el nombre del grupo de colaboración, si lo hubiereCongenital lactic acidosis (CLA) is a rare condition in most instances due to a range of inborn errors of metabolism that result in defective mitochondrial function. Even though the implementation of next generation sequencing has been rapid, the diagnosis rate for this highly heterogeneous allelic condition remains low. The present work reports our group’s experience of using a clinical/biochemical analysis system in conjunction with genetic findings that facilitates the taking of timely clinical decisions with minimum need for invasive procedures. The system’s workflow combines different metabolomics datasets and phenotypic information with the results of clinical exome sequencing and/or RNA analysis. The system’s use detected genetic variants in 64% of a cohort of 39 CLA-patients; these variants, 14 of which were novel, were found in 19 different nuclear and two mitochondrial genes. For patients with variants of unknown significance, the genetic analysis was combined with functional genetic and/or bioenergetics analyses in an attempt to detect pathogenicity. Our results warranted subsequent testing of antisense therapy to rescue the abnormal splicing in cultures of fibroblasts from a patient with a defective GFM1 gene. The discussed system facilitates the diagnosis of CLA by avoiding the need to use invasive techniques and increase our knowledge of the causes of this conditio

Generation and characterization of a human iPSC line (UAMi005-A) from a patient with nonketotic hyperglycinemia due to mutations in the GLDC gene

A human induced pluripotent stem cell (iPSC) line was generated from fibroblasts of a patient with nonketotic hyperglycinemia bearing the biallelic changes c.1742C > G (p.Pro581Arg) and c.2368C > T (p.Arg790Trp) in the GLDC gene. Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were delivered using a non-integrative method based on the Sendai virus. Once established, iPSCs have shown full pluripotency, differentiation capacity and genetic stability. This cellular model provides a good resource for disease modeling and drug discoveryResearch reported in this work was funded by Grants of Spanish Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) PI16/00573, and Fundación Isabel Gemio- Fundación La Caixa (LCF/PR/PR16/11110018). The authors thank the Cytogenetic unit from Centro Nacional de Investigaciones Oncológicas (CNIO) for its excellent technical assistance. Centro de Biología Molecular Severo Ochoa receives an institutional grant from Fundación Ramón Areces. LAC is a PhD student funded by the Asociación Española para el Estudio de Metabolopatías Congénitas (AEPMEC). ALM is a postdoctoral researcher of Comunidad Autónoma de Madrid (PEJD-2017-POST/BMD-3671). EAB is a PhD student funded by the FPU program of the Spanish Ministry of Science, Innovation and Universities (FPU15/02923